Table 1.
Gene-level associations with glucose and HbA1c levels.
| Gene | Variant set | Title | p-value | Effect (SD) | Effect (IFCC units) | 95% CI− (IFCC units) | 95% CI+ (IFCC units) | IFCC units | n carrier measured |
|---|---|---|---|---|---|---|---|---|---|
| GCK | pLOF | Glucose | 1.56 × 10–9 | 1.00 | 1.24 | 0.84 | 1.65 | mmol/L | 35 |
| GIGYF1 | pLOF | Glucose | 4.42 × 10–12 | 0.62 | 0.77 | 0.55 | 0.98 | mmol/L | 121 |
| GCK | missense | Glucose | 6.15 × 10–11 | 0.49 | 0.61 | 0.42 | 0.79 | mmol/L | 173 |
| G6PC2 | missense | Glucose | 4.62 × 10–83 | − 0.27 | − 0.33 | − 0.36 | − 0.3 | mmol/L | 5128 |
| GCK | pLOF | HbA1c | 2.64 × 10–17 | 1.29 | 8.75 | 6.73 | 10.78 | mmol/mol | 38 |
| GIGYF1 | pLOF | HbA1c | 1.28 × 10–14 | 0.64 | 4.33 | 3.23 | 5.43 | mmol/mol | 129 |
| HNF1A | pLOF | HbA1c | 2.14 × 10–7 | 0.59 | 4.01 | 2.50 | 5.53 | mmol/mol | 68 |
| TNRC6B | pLOF | HbA1c | 2.36 × 10–7 | 0.58 | 3.94 | 2.45 | 5.43 | mmol/mol | 70 |
| RHAG | pLOF | HbA1c | 3.31 × 10–34 | − 0.86 | − 5.81 | − 6.75 | − 4.88 | mmol/mol | 179 |
| EPB41 | pLOF | HbA1c | 3.14 × 10–17 | − 0.53 | − 3.58 | − 4.41 | − 2.75 | mmol/mol | 226 |
| PTPRH | pLOF | HbA1c | 4.39 × 10–10 | 0.11 | 0.74 | 0.51 | 0.97 | mmol/mol | 2924 |
| APOB | pLOF | HbA1c | 6.94 × 10–8 | 0.23 | 1.57 | 1.00 | 2.15 | mmol/mol | 478 |
| PLD1 | pLOF | HbA1c | 2.99 × 10–7 | 0.23 | 1.56 | 0.96 | 2.16 | mmol/mol | 438 |
| EPB42 | pLOF | HbA1c | 6.11 × 10–7 | − 0.31 | − 2.08 | − 2.90 | − 1.26 | mmol/mol | 234 |
| GCK | missense | HbA1c | 1.86 × 10–17 | 0.56 | 3.83 | 2.94 | 4.71 | mmol/mol | 201 |
| G6PC2 | missense | HbA1c | 6.71 × 10–45 | − 0.18 | − 1.21 | − 1.38 | − 1.04 | mmol/mol | 5574 |
| PFAS | missense | HbA1c | 2.09 × 10–8 | − 0.05 | − 0.32 | − 0.44 | − 0.21 | mmol/mol | 12,621 |
| PDX1 | missense | HbA1c | 2.54 × 10–7 | 0.06 | 0.41 | 0.25 | 0.56 | mmol/mol | 6694 |
| PIEZO1 | missense | HbA1c | 1.0 × 10–132 | − 0.15 | − 1.00 | − 1.07 | − 0.92 | mmol/mol | 26,726 |
| AMPD3 | missense | HbA1c | 7.28 × 10–34 | 0.13 | 0.86 | 0.72 | 1.00 | mmol/mol | 8258 |
| PFKM | missense | HbA1c | 2.16 × 10–28 | − 0.28 | − 1.92 | − 2.26 | − 1.58 | mmol/mol | 1353 |
| ANK1 | missense | HbA1c | 3.12 × 10–19 | − 0.13 | − 0.87 | − 1.06 | − 0.68 | mmol/mol | 4342 |
| PFKL | missense | HbA1c | 2.69 × 10–14 | 0.10 | 0.68 | 0.50 | 0.85 | mmol/mol | 5245 |
| AXL | missense | HbA1c | 4.11 × 10–12 | − 0.08 | − 0.54 | − 0.69 | − 0.39 | mmol/mol | 6827 |
| LCAT | missense | HbA1c | 1.29 × 10–11 | − 0.27 | − 1.82 | − 2.34 | − 1.29 | mmol/mol | 565 |
| PLA2G12A | missense | HbA1c | 5.74 × 10–11 | − 0.08 | − 0.51 | − 0.67 | − 0.36 | mmol/mol | 6761 |
| PLD1 | missense | HbA1c | 1.51 × 10–10 | 0.08 | 0.57 | 0.40 | 0.75 | mmol/mol | 5180 |
| APEH | missense | HbA1c | 1.86 × 10–10 | 0.29 | 1.96 | 1.36 | 2.57 | mmol/mol | 429 |
| TNFRSF13B | missense | HbA1c | 4.63 × 10–9 | − 0.08 | − 0.51 | − 0.68 | − 0.34 | mmol/mol | 5470 |
| BLVRB | missense | HbA1c | 2.53 × 10–8 | − 0.07 | − 0.48 | − 0.65 | − 0.31 | mmol/mol | 5533 |
| TMC8 | missense | HbA1c | 3.01 × 10–8 | 0.11 | 0.77 | 0.50 | 1.05 | mmol/mol | 2095 |
| HK1 | missense | HbA1c | 1.08 × 10–7 | − 0.16 | − 1.08 | − 1.48 | − 0.68 | mmol/mol | 988 |
| SLC4A1 | missense | HbA1c | 1.76 × 10–7 | − 0.15 | − 1.04 | − 1.43 | − 0.65 | mmol/mol | 1025 |
| TFR2 | missense | HbA1c | 4.24 × 10–7 | − 0.12 | − 0.84 | − 1.16 | − 0.51 | mmol/mol | 1491 |
| CARHSP1 | missense | HbA1c | 6.78 × 10–7 | − 0.13 | − 0.86 | − 1.20 | − 0.52 | mmol/mol | 1360 |
pLOF or damaging missense variants (CADD score ≥ 25) were aggregated per gene. The effect is shown in standard deviations (SD) of transformed values as well as in International Federation of Clinical Chemistry (IFCC) units.
CI confidence interval.